Daniela M. Proca

Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers.

Distinguishing hepatocellular carcinoma (HCC) from metastatic adenocarcinoma (MA) and cholangiocarcinoma (CC) can, at times, be difficult and sometimes requires immunohistochemical analysis. Recently, MOC31, an antibody directed against a cell surface glycoprotein, has been shown to be useful in separating HCC from both MA and CC; however, no study has compared MOC31 and other frequently used immunostains. We compare MOC31 with other commonly used immunostains for HCC, MA, and CC. Formalin-fixed, paraffin-embedded tissue sections from 57 previously characterized hepatic neoplasms (13 HCC, 14 CC, 3 combined HCC-CC, and 27 MA) were immunostained with antibodies directed against MOC31, cytokeratin (CK) 7, CK20, α-fetoprotein (AFP), polyclonal carcinoembryonic antigen, Ber-EP4, and Factor XIII-A. Two pathologists reviewed slides, and positivity was defined as more than 1% of cells staining with the appropriate pattern. Positive MOC31 immunostaining was seen in 0 of 13 HCC, 13 of 14 CC, 3 of 3 HCC-CC, and 27 of 27 MA; the staining was strong and diffuse. CK20 reactivity was observed in 0 of 13 HCC, 2 of 14 CC, 0 of 3 HCC-CC, and 12 of 27 MA; CK7 immunostained 4 of 13 HCC, 13 of 14 CC, 3 of 3 HCC-CC, and 15 of 27 MA; AFP was detected in 4 of 13 HCC and 2 of 3 HCC-CC, whereas all CC and MA were negative; polyclonal carcinoembryonic antigen showed immunoreactivity in 12 of 13 HCC and 3 of 3 HCC-CC in a canalicular pattern, whereas diffuse positivity was identified in 13 of 14 CC and 26 of 27 MA; Ber-EP4 immunostained 1 of 13 HCC, 14 of 14 CC, 2 of 3 HCC-CC, and 26 of 27 MA; and Factor XIII-A was negative in all HCC, CC, and MA. MOC31 expression distinguished HCC from adenocarcinoma in 56 of 57 cases. AFP was specific for HCC but was not sensitive. CK7 and CK20 have limited utility in distinguishing HCC from CC or MA, and Factor XIII-A is not useful. Ber-EP4 staining was similar to MOC31, but one HCC did stain with Ber-EP4. Polyclonal CEA yields similar numerical results as MOC31, but the focal nature of the staining and occasional difficulty in evaluating the pattern can make interpretation problematic. We conclude that MOC31 should be a component of the immunohistochemical panel to distinguish HCC from CC and MA.

Frozen section diagnosis of pancreatic lesions.

BACKGROUND The clinical and radiologic diagnosis of pancreatic cancer and the safety of pancreatic resections have improved. These improvements, together with the indication for resection in some cases of complicated chronic pancreatitis, have reduced the necessity for confirmed preoperative tissue diagnosis. We investigated the clinical use and accuracy of frozen section diagnosis for pancreatic lesions. DESIGN We searched archival files for the years 1989-2000 for patients with pancreatic lesions who had received a diagnosis based on frozen section results. We compared the diagnosis of all frozen section slides with that of the permanent sections and reviewed the clinical follow-up notes. We evaluated histologic features useful in differentiating between malignant and benign pancreatic lesions. RESULTS A total of 538 patients underwent surgical biopsy and/or resection for suspected pancreatic lesions. Frozen section was requested in 131 cases (284 frozen sections). Ninety cases had frozen section of the pancreatic lesions, 70 cases had frozen section of metastatic sites, and 29 cases had frozen section of surgical margins. Of the 90 cases in which frozen section of the pancreatic lesions was requested, malignancy was diagnosed in 44, a benign lesion was diagnosed in 37, and the diagnosis was atypical and deferred in 9. In total, 3 false-negative frozen sections and 1 false-positive frozen section were identified for respective rates of 1.2% and 0.3%. In all cases in which the frozen section diagnosis was deferred or was inconsistent with the operative impression, and the surgeon acted on his/her impression, the operative diagnoses were subsequently confirmed by additional permanent sections and/or clinical follow-up. The most useful histologic features for the diagnosis of pancreatic adenocarcinoma in frozen sections were variation in nuclear size of at least 4:1, disorganized duct distribution, incomplete duct lumen, and infiltrating single cells. CONCLUSIONS Frozen sections are useful in conjunction with the impression at surgery for the management of patients with pancreatic lesions. Frozen sections of resection margins were 100% accurate; frozen sections of pancreatic lesions or metastatic sites were accurate in 98.3% of cases. We found an acceptable rate of deferred frozen section (6.6%). The experienced surgeons impression of malignancy is reliable in cases in which frozen section is deferred or has negative findings.

MOC31 immunoreactivity in primary and metastatic carcinoma of the liver. Report of findings and review of other utilized markers.

Differentiating between primary tumors of the liver and metastatic lesions can, at times, be difficult. Various histochemical and immunohistochemical methods have been used in an effort to better delineate between hepatocellular carcinoma (HCC), especially the microglandular variant, primary cholangiocarcinoma, and metastatic adenocarcinoma; these ancillary studies can yield less than satisfactory results. Recently, anti-MOC31, a monoclonal antibody directed against a cell surface glycoprotein, has been shown to be helpful in distinguishing between adenocarcinoma and mesothelioma. This study addresses whether this antibody might be helpful in distinguishing between HCC, primary cholangiocarcinoma, and metastatic adenocarcinoma in the liver. Formalin-fixed, paraffin-embedded tissue sections from 15 HCC (including 10 microglandular variants), 14 primary cholangiocarcinomas, and 33 metastatic adenocarcinomas (7 colon, 1 lung, 8 breast, 4 GE jct/gastric, 9 pancreas, 2 small intestine, 1 renal, 1 ovary) were immunostained with anti-MOC 31 (1:40, Dako) after protease digestion and biotin block using a modified ABC technique. Positive staining was limited to membrane based reactivity; controls stained appropriately. Immunoreactivity for MOC31 was observed in 14 of 14 cholangiocarcinomas and 33 of 33 metastatic tumors. Staining was diffuse, intense, and readily interpretable, with rare exceptions. All 15 cases of HCC were negative. We conclude that cholangiocarcinoma and metastatic adenocarcinoma from a variety of sites express MOC31; HCC is uniformly negative for this marker. Anti-MOC31 may prove useful in the evaluation of liver neoplasms where primary hepatocellular and adenocarcinoma enter the differential diagnosis; it is not useful in separating primary cholangiocarcinoma from metastatic adenocarcinoma.

Exfoliative cytology of neuroendocrine small cell carcinoma of the endometrium : A report of two cases

BACKGROUND In the female genital tract, neuroendocrine small cell carcinoma can occur in the endometrium as well as the cervix, ovary and vagina. This tumor has a high propensity for systemic spread and a poor prognosis. Small cell carcinoma of the endometrium is cytologically identical to its counterparts in the lung and other sites. Its characteristic appearance in a cervicovaginal smear should raise concern about small cell carcinoma. Other tumors of the uterus should be considered in the differential diagnosis, including adenocarcinoma with neuroendocrine features, small cell nonkeratinizing squamous cell carcinoma, endometrial stromal sarcoma, rhabdomyosarcoma, primitive neuroectodermal tumor, non-Hodgkins lymphoma and metastatic breast carcinoma. CASES Case 1 was a 59-year-old, white female, and case 2 was a 47-year-old, white female. Both patients presented with vaginal bleeding. The Papanicolaou smears in both cases had similar, characteristic exfoliative cytology. The tumor cells were small and either single or arranged in groups and files. They had barely visible cytoplasm, darkly staining nuclei with finely stippled chromatin, and inconspicuous nucleoli. The characteristic molding of the nuclei was also present. Immuno-histochemical staining for neuron-specific enolase and synaptophysin was positive in tissue sections. Pancytokeratin, vimentin, muscle-specific actin, desmin, alpha-fetoprotein, S-100, glial fibrillary acid protein, common leukocyte antigen and chromogranin were negative. CONCLUSION When a uterine small cell carcinoma is suspected in a cervicovaginal smear, the similarity of cervical and endometrial small cell carcinoma requires a differential curettage and immunohistochemical demonstration of neuroendocrine differentiation in order to arrive at the final diagnosis.

Smooth muscle tumor of the pleura. A case report and review of the literature.

Smooth muscle tumors of the serosal membranes are extremely rare and have received little attention in the literature. To the best of our knowledge, only 1 published series of 5 pleural smooth muscle neoplasms has been published to date. We describe a primary pleural neoplasm with smooth muscle differentiation documented by light microscopy, immunohistochemistry, and electron microscopy. This tumor originated in the parietal pleura in a 32-year-old white man and was diagnosed incidentally by chest radiography; the diagnosis was confirmed by magnetic resonance imaging and biopsy. Four years later, the tumor was noted to have increased in size and disseminated into the chest wall as a separate circumscribed mass located in the pectoral muscle. Both masses were resected and diagnosed as smooth muscle tumors. We conclude that smooth muscle tumor of the pleura is a well-defined entity with a low, but definite malignant potential; therefore, we recommend complete resection and long-term follow-up for all patients.

Major Pancreatic Resections for Chronic Pancreatitis

OBJECTIVE Indications for major pancreatic resections have been expanded to include complicated chronic pancreatitis (CP). We assessed clinical findings and outcomes and evaluated histology in patients who had major pancreatic resections for CP. We also determined if histologic findings were associated with persistent postoperative pain. DESIGN We reviewed charts and slides from 44 patients who underwent major pancreatic resections for CP between 1989 and 1999. RESULTS The etiology for disease included alcohol (n = 15), hereditary (n = 5), idiopathic (n = 6), pancreas divisum (n = 3), stricture (n = 2), trauma (n = 2), systemic lupus erythematosus (n = 1), and unknown (n = 10). Patients included 20 men and 24 women; ages ranged from 22 to 76 years. Perioperative mortality and morbidity were 0% and 4.5%, respectively. Persistent pain was present in 25 (57%) of the 44 patients, and pain was encountered more frequently in patients with alcoholic pancreatitis (67%) versus other etiologies (52%), and in those who underwent Whipple/Beger or total resections (68%) versus distal or subtotal pancreatectomy (42%). Metaplastic changes were present in 14 cases, and ductal atypia was seen in 9 cases. No malignancies were found. Acinar necrosis and acute inflammation were seen more often in patients with persistent pain than in those who were pain free (P =.081). CONCLUSION Major pancreatic resection for CP can be performed with low morbidity and mortality. This procedure relieves pain in nearly half the patients. There is a wide spectrum of histopathologic changes seen in CP, including ductal atypia and metaplastic changes. Acute exacerbations of CP identified histologically at the time of surgery and alcohol as etiology for CP may be associated more frequently with intractable pain.

Anaplastic large cell lymphoma in a human immunodeficiency virus-positive patient with cytologic findings in bladder wash: a case report.

BACKGROUND Anaplastic large cell lymphoma (ALCL) (Ki-1/CD-30 positive) is an uncommon lymphoproliferative disorder that may be of T cell or null cell type. ALCL has been reported in fine needle aspirations of lymph nodes and pleural or peritoneal fluid cytology. In human immunodeficiency virus (HIV)-positive patients, ALCL appears to be more common and run a more aggressive course. CASE A 39-year-old black man, seropositive for HIV, presented with acute renal failure secondary to bilateral ureteral obstruction by a pelvic mass involving the urinary bladder. Bladder wash cytology and subsequent biopsy of the mass were diagnostic of ALCL. The ALCL was CD30+ and null cell type, with negative CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD45, CD79a, ALK-1, granzyme B, cytokeratin (AE1/AE3), placental alkaline phosphatase (PLAP) and S-100. The patient expired 9 months after the diagnosis, despite aggressive therapy. CONCLUSION This is a rare occurrence of ALCL (CD 30 positive, null cell type) in the urinary bladder in an HIV+ patient. Presumptive diagnosis was made by bladder wash cytology and subsequently confirmed by biopsy. Urinary cytologic examination is a useful diagnostic tool. In HIV+/immunosuppressed patients with urinary symptoms and an obstructive mass, ALCL should be considered in the differential diagnosis.

High grade squamous intraepithelial lesion in inmates from Ohio : Cervical screening and biopsy follow-up

Background Cervical carcinoma remains the second leading cause of cancer death in women worldwide and sexual behavior is regarded as the main contributing factor. We studied cervical cytology screening with surgical biopsy follow-up in women prisoners and compared the findings to those in the general population. Methods We reviewed 1024 conventional cervical smears, 73 cervical biopsies and 2 loop electrosurgical excision procedure (LEEP) specimens referred to us from the Correctional Center in Columbus, Ohio during a 12-month period. The results were compared to 40,993 Pap smears from the general population for the same 12-month period. Results High grade squamous intraepithelial lesion (HGSIL) was diagnosed in 1.3% of the cervical smears from the inmate population versus 0.6% in the general population (p < 0.01). The unsatisfactory rate was 1.6% compared to 0.3% in the general population (p < 0.01). Among the study population, follow-up tissue diagnosis was obtained in 24.3% of the abnormal cytology results (ASCUS, LGSIL, and HGSIL). Of the HGSIL Pap smears, 61.5% had a subsequent tissue diagnosis. Thirty-nine biopsies (52% of the all inmate biopsies and LEEP) showed CIN II/III (cervical intraepithelial neoplasia II/III). Eight of these thirty-nine follow-up biopsies diagnosed as CIN II/III had a previous cervical cytology diagnosis of ASCUS. The average age for HGSIL was 30.5 years (S.D. = 5.7) and for low grade squamous intraepithelial lesion (LGSIL) was 27.2 years (S.D. = 6.1). Conclusion A significantly higher prevalence of HGSIL cervical cytology and unsatisfactory smears was encountered in female inmates, with tissue follow-up performed in less than two thirds of the patients with HGSIL. These results are in keeping with data available in the literature suggesting that the inmate population is high-risk and may be subject to less screening and tissue follow-up than the general population. Clinicians should proceed with urgency to improve screening and follow-up with treatment. The inmate population should be targeted for HPV vaccination promptly after FDA approval.

Exfoliative Cytology of Lymphoepitheliomalike Carcinoma of the Uterine Cervix

BACKGROUND Lymphoepitheliomalike carcinomas (LECs) are morphologically similar to undifferentiated nasopharyngeal carcinoma but occur at sites other than the nasopharynx. They rarely occur in the uterine cervix. Sixty-five cases of LEC of the cervix have been published to date, and the pitfalls of histopathologic interpretation have been discussed. This undifferentiated carcinoma with a prominent lymphocytic infiltrate represents a challenge for the pathologist examining a scant cervical biopsy or Pap smear. Distinguishing LEC as a separate entity is important. Despite the fact that the epithelial component is poorly differentiated, this neoplasm is associated with a lower frequency of lymph node metastases, is potentially radiosensitive and has a better prognosis. Although mentioned in passing in several papers, the exfoliative cytology of this cervical neoplasm has not been adequately discussed. We report the cytologic features of LEC in cervical smears obtained from two patients. CASES The first patient presented with menometrorrhagia and postcoital bleeding. The cervical smear taken at the time of presentation was reported as unsatisfactory for evaluation. ASCUS was diagnosed on a vaginal smear obtained one year earlier. The second patient presented with a complaint of postcoital bleeding. A cervical smear and the cervical biopsy taken at the time of presentation were reported as ASCUS and high grade dysplasia versus carcinoma, respectively. A retrospective review of the cervical smears revealed rare malignant cells occurring singly or in small groups. The tumor cells had a high nuclear/cytoplasmic ratio, irregular nuclear membrane and hyperchromatic nuclei with coarse chromatin and were obscured by heavy inflammation and blood. The background resembled that of a menstrual smear. CONCLUSION The diagnosis of LEC of the cervix is often made on a loop electrical excision procedure or on a hysterectomy specimen. The presence of heavy inflammation and blood, which can obscure the malignant nature of the cells, presents the cytopathologist with a challenging diagnosis of LEC in cervical smears. In view of the prognostic implications, it is desirable for the pathologist to classify LEC as a distinct entity.

Pancreatic endocrine tumors-c-erb B2 (Her-2/neu), bcl-2, and p-53 immunohistochemical testing and their value in assessing prognosis.

IntroductionIn an attempt to identify better prognostic factors, and the genetic basis of pancreatic endocrine tumors (PETs), we evaluated immunohistochemical reactivity for c-erb B2 (Her-2/neu), bcl-2, and p53. Methods and MaterialsTwo pathologists reviewed hematoxylin and eosin slides and immunohistochemical stains from 28 cases, 27 tumors and 1 nesidioblastosis. Using WHO criteria for malignancy (presence of local or lymphovascular invasion and/or metastases), cases were divided into malignant (20 cases) and benign or uncertain (8 cases). Nuclear staining in >1% of cells was considered positive for p53 and bcl-2, whereas membranous staining was considered positive for c-erb B2 (Her-2/neu). ResultsAll cases were nonimmunoreactive with anti-c-erb B2 (Her-2/neu), but focal granular or diffuse cytoplasmic staining was seen in occasional neoplasms. One malignant PET showed reactivity with anti-p53, whereas all others were negative. bcl-2 reactivity was identified in 15/28 cases: 9/20 malignant PETs and 6/8 others were positive. Conclusionsc-erb B2 (Her-2/neu) and p53 are not useful prognostic factors in PET. c-erb B2 (Her-2/neu) staining must be carefully evaluated to avoid the misinterpretation of artifactual/background staining. bcl-2 is occasionally expressed in PET, but the significance of this finding is still to be determined.